Humic substance-based antivirals: antiretroviral activity, mechanisms of action, and impact on mucosal immunityстатья

Статья опубликована в высокорейтинговом журнале

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Дата последнего поиска статьи во внешних источниках: 10 апреля 2018 г.

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[1] Humic substance-based antivirals: antiretroviral activity, mechanisms of action, and impact on mucosal immunity / Y. Zhernov, E. Karamov, I. Perminova et al. // Allergy. — 2017. — Vol. 72. — P. 164–165. Introduction: Secondary immunodeficiency is the loss of immune function as a result of exposure to disease agents, immunosuppression, or aging. All secondary immunodeficiencies have been outdone by AIDS that is caused by HIV. HIV directly infects a small number of Th cells, and also impairs other immune system responses indirectly. Despite the wide application of HAART, the number of HIVpositive patients continues to grow steadily. This shows an urgent need for a directed search for new antiviral drugs against HIV. 164 | ABSTRACTS Objectives: The purpose of this study was to investigate the antiretroviral activity of humic substances (HS), its mechanisms of action, and impact on mucosal immunity. The evaluation of antiretroviral efficacy of HS was performed using HIV-1 BRU and different target cells (MT-4, CEM-SS). The level of virus replication was detected by p24 HIV-1 antigen ELISA. Mechanisms of action were evaluated in a Time of addition assay. Mucosal immunostimulatory activity of HS evaluated in several in vitro cell models (PBMC, macrophages and dendritic cells). Cytotoxicity was determined using the MTT assay. Results: The results showed that the HS fractions exhibited a distinct antiviral activity within the concentration range from 0.78 ug/ mL to 100 ug/mL with respect to HIV-1. All fractions of HS from peloids within the studied range of concentrations did not display pronounced cytotoxicity. Time of addition assay show that HS have antiviral activity at the stage of HIV fusion, and at the stage of reverse transcription of DNA to RNA, and at the stage of integration of viral DNA into the genome of the host cell. HS increased lymphocyte proliferation of phytohaemagglutinin A (PHA) and pokeweed mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro from concentrations of 10 to 100 ug/mL. HS inhibited the release of TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL at 50 ug/mL. Conclusions: The low cytotoxicity and high antiretroviral activity of HS indicate that these substances hold significant promise as safe and efficacious antiviral drugs for the treatment of secondary immunodeficiency, such as HIV infection. The ability of HS to interfere with multiple stages of the HIV replication cycle of is viewed as an added benefit suggesting potential for further development as antiviral drugs. 0487 | Functional characterization of T helper cells in a cohort of common variable immunodeficiency patients Milota T; Kayserova J; Zachova R; Rataj M; Sediva A 2nd Faculty of Medicine Charles University and University Hospital in Motol, Prague, Czech Republic Introduction: Common Variable Immunodeficiency (CVID) is a heterogenous group of disorders characterized by impaired immunoglobulin production and dysregulation of immune system. Dysregulation may manifest as lymphoproliferative, granulomatous or autoimmune diseases. Autoimmunity occurs in 25-30% of CVID patients according to available literature sources. The underlying mechanisms have not been entirely revealed yet. Alterations in innate as well as adaptive immunity have been described, however, only few studies regarded T cell compartment were carried out. Particularly abnormalities in T cell development were previously reported such as reduction of recent thymic emigrants or reduction of CD4+ T cells (primarily naive CD4+ T cells), specifically in CVID patients with autoimmune complications. Moreover, there is also lack of information about T-cells (Th cells respectively) functions. Therefore, we initiated our study to characterize predominant immune response (Th1, Th2 or Th17) and corresponding cytokine production (IFN-gamma, IL-5, IL-17), expression of transcriptional factors (T-Bet, GATA-3, ROR-gamma) and chemokine receptors (CXCR3, CRTH2, CCR6) and to assess expression of activation markers (CD69, CD154 and HLA-DR) in a cohort of CVID patients. Objectives: PBMC (peripheral blood mononucler cells) were izolated from whole peripheral blood using Ficoll-Paque gradient. After isolation PBMC were stimulated with ionomycin and PMA (Phorbol myristate acetate) for 6 hours. We measured expression and production of CD3, CD4, CD8, CD69, CD154, HLA-DR, CXCR3, CRTH2, CCR6, T-Bet, GATA-3, ROR-gamma, IFN-gamma, IL-5, IL-17 using standard flowcytometric protocols for cell surface membrane and intracellular markers and cytokine detection. All flowcytometric data were statistically analyzed Results: Together 20 CVID patients with/without autoimmune or lymphoproliferative complications were analyzed. We compared the results of CVID patients cohort to corresponding sex and age related cohort of healthy controls. There are significant differences in the intracellular cytokine production and expression of assessed markers mentioned above. Conclusions: We found skewing in the character of immune response and in the expression of activation markers in our cohort of CVID patients in comparison to healthy controls. [ DOI ]

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